5-Hydroxytryptamine Modulates Migration, Cytokine and Chemokine Release and T-Cell Priming Capacity of Dendritic Cells In Vitro and In Vivo

Beside its well described role in the central and peripheral nervous system 5-hydroxytryptamine (5-HT), commonly known as serotonin, is also a potent immuno-modulator. Serotoninergic receptors (5-HTR) are expressed by a broad range of inflammatory cell types, including dendritic cells (DCs). In this study, we aimed to further characterize the immuno-biological properties of serotoninergic receptors on human monocyte-derived DCs. 5-HT was able to induce oriented migration in immature but not in LPS-matured DCs via activation of 5-HTR1 and 5-HTR2 receptor subtypes. Accordingly, 5-HT also increased migration of pulmonary DCs to draining lymph nodes in vivo. By binding to 5-HTR3, 5-HTR4 and 5-HTR7 receptors, 5-HT up-regulated production of the pro-inflammatory cytokine IL-6. Additionally, 5-HT influenced chemokine release by human monocyte-derived DCs: production of the potent Th1 chemoattractant IP-10/CXCL10 was inhibited in mature DCs, whereas CCL22/MDC secretion was up-regulated in both immature and mature DCs. Furthermore, DCs matured in the presence of 5-HT switched to a high IL-10 and low IL-12p70 secreting phenotype. Consistently, 5-HT favoured the outcome of a Th2 immune response both in vitro and in vivo. In summary, our study shows that 5-HT is a potent regulator of human dendritic cell function, and that targeting serotoninergic receptors might be a promising approach for the treatment of inflammatory disorders

An overlooked connection: serotonergic mediation of estrogen-related physiology and pathology

BACKGROUND: In humans, serotonin has typically been investigated as a neurotransmitter. However, serotonin also functions as a hormone across animal phyla, including those lacking an organized central nervous system. This hormonal action allows serotonin to have physiological consequences in systems outside the central nervous system. Fluctuations in estrogen levels over the lifespan and during ovarian cycles cause predictable changes in serotonin systems in female mammals. DISCUSSION: We hypothesize that some of the physiological effects attributed to estrogen may be a consequence of estrogen-related changes in serotonin efficacy and receptor distribution. Here, we integrate data from endocrinology, molecular biology, neuroscience, and epidemiology to propose that serotonin may mediate the effects of estrogen. In the central nervous system, estrogen influences pain transmission, headache, dizziness, nausea, and depression, all of which are known to be a consequence of serotonergic signaling. Outside of the central nervous system, estrogen produces changes in bone density, vascular function, and immune cell self-recognition and activation that are consistent with serotonin's effects. For breast cancer risk, our hypothesis predicts heretofore unexplained observations of the opposing effects of obesity pre- and post-menopause and the increase following treatment with hormone replacement therapy using medroxyprogesterone. SUMMARY: Serotonergic mediation of estrogen has important clinical implications and warrants further evaluation

Serotonin and GI Disorders: An Update on Clinical and Experimental Studies

The gastrointestinal (GI) tract is the largest producer of serotonin (5-hydroxytryptamine (5-HT)) in the body, and as such it is intimately connected with GI function and physiology. 5-HT produced by enterochromaffin (EC) cells is an important enteric mucosal signaling molecule and has been implicated in a number of GI diseases, including inflammatory bowel disease and functional disorders such as irritable bowel syndrome. This review will focus on what is known of basic 5-HT physiology and also on the emerging evidence for its novel role in activation of immune response and inflammation in the gut. Utilizing pubmed.gov, search terms such as “5-HT,” “EC cell,” and “colitis,” as well as pertinent reviews, were used to develop a brief overview of EC cell biology and the association between 5-HT and various GI disorders. It is the aim of this review to provide the readers with an update on EC cell biology and current understanding on the role of 5-HT in GI disorders specifically in inflammatory conditions

Characterization of transport properties variations with magnetic field and temperature of ITER-candidate NbTi strands

While the International Thermonuclear Experimental Reactor (ITER) conceptual design retained the Nb3Sn for toroidal field (TF) and central solenoid (CS) coils, the low working field (around 6 T) promoted the choice of NbTi for the poloidal field (PF) coils. EU has carried out the experimental study of industrial NbTi strands and cables with different internal structures in order to choose the one which generate the lowest losses when used in the PF operating conditions (i.e. pulsed field). CEA has contributed to this project through the experimental study of the transport properties variations with respect to magnetic field and temperature of two candidate strands. One of them contains an internal CuNi barrier and the other is Ni-plated. A homemade cryostat is used to control the temperature of the sample which is wound on a VAMAS-like mandrel. J(c) measurements are presented here and subsequently the parameters deduced from scaling laws and their variation with temperature between 4.2 and 7 K and with field up to I 1 T. A comparison between the two strands characteristics and ITER PF coils criteria is also discussed. The results are in good agreement with literature and lie inside an acceptable range in spite of some discrepancy with the ITER PF criteria: a recent thermo-hydraulic simulation confirmed it. In the future, this study, completed by AC losses measurements on cabled strands, should help to optimise the strands performances below the ITER PF security margins. (C) 2002 Published by Elsevier Science B.V

Characterization of industrial NbTi strands at variable field for JT-60SA toroidal field coils

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Influence of bending strain on the critical properties of jacketed Nb₃Sn strands for ITER

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Using the HELIOS facility for assessment of bundle-jacket thermal coupling in a CICC

CHATS on Applied Superconductivity Workshop (CHAT-AS), Dept Elect, Elect & Informat Engn, Bologna, ITALY, SEP 14-16, 2015International audienceIn a Cable In Conduit Conductor (CICC) cooled by forced circulation of supercritical helium, the heat exchange in the bundle region can play a significant role for conductor safe operation, while remaining a quite uncertain parameter. Heat exchange between bundle and jacket depends on the relative contributions of convective heat transfer due to the helium flow inside the bundle and of thermal resistance due to the wrappings between the cable and the conduit. In order to qualify this thermal coupling at realistic operating conditions, a dedicated experiment on a 1.2 m sample of ITER Toroidal Field (TF) dummy conductor was designed and performed in the HELIOS test facility at CEA Grenoble. Several methods were envisaged, and the choice was made to assess bundle jacket heat transfer coefficient by measuring the temperature of a solid copper cylinder inserted over the conductor jacket and submitted to heat deposition on its outer surface. The mock-up was manufactured and tested in spring 2015. Bundle jacket heat transfer coefficient was found in the range 300-500 W m(-2) K-1. Results analysis suggests that the order of magnitude of convective heat transfer coefficient inside bundle is closer to Colburn-Reynolds analogy than to Dittus-Boelter correlation, and that bundle jacket thermal coupling is mainly limited by thermal resistance due to wrappings. A model based on an equivalent layer of stagnant helium between wraps and jacket was proposed and showed a good consistency with the experiment, with relevant values for the helium layer thickness. (C) 2016 Elsevier Ltd. All rights reserved

Contribution to the study of superconducting magnetic systems in the frame of fusion projects

This report is a presentation of all the 55 publications made by the Magnet Group of the "Department de Recherches sur la Fusion Contolee" during the 94-99 period. These publications have been made mainly in the frame of EURATOM contracts and tasks for ITER